Study on the Platform for Ophthalmic Drug Development and Active Ingredients Production
| Autor: | Hsing-Yu Pan, 潘星佑 |
|---|---|
| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 Dry eye is a common eye disease in developed countries and the prevalence increases with age. Dry eye is caused by inadequate quality or quantity of secreted proteins in tears, and many cause dryness, redness, burning and other symptoms. There is still an unmet medical need in dry eye disease. In this study, we try to establish an ophthalmic pharmaceutical drug development platform, and looking for potential drugs in the treatment of dry eye. Active fraction isolated from traditional herb. It has unique mechanism and might have the potential to become a drug for dry eye disease. In this study, we treated active fraction to human corneal epithelium cells at the concentration of 0.4,2 and 10µg/ml for 24 hours. It increases the mitochondrial activity and enhanced erythropoietin (EPO), PGC-1α and Sirt1 gene expression in HCE cell. We further used benzalkonium chloride as a damage agent in HCE cell, and found that active fraction increased cell viability and mitochondrial activity after 24 and 48 hours treatment. In lacrimal gland organ culture, active fraction treatment promoted the gene expression of EPO, PGC-1α, Sirt1, BDNF and NGF. In addition, we used benzalkonium chloride as dry eye inducing agent in our mice model. We treated the mice with eyes drops containing active fraction 2,5 and 10 µg / ml three times a day, and found such treatment restored tear secretion and increased EPO gene and protein expression in lacrimal gland. Therefore, our data highlighted that active fraction can activate EPO, PGC-1α, Sirt1, BDNF and NGF in lacrimal gland, and has the potential to become a therapeutic drug candidate for dry eye disease. The ingredient of natural products has been a very important part of drug development, and how to provide a stable source has become an important issue in modern drug development. We established chemical synthesis active fraction for five steps. The final overall yield is 3.4%. On the other hand, we also promote the production of active fraction from plant stem cells by addition of different stimulus. We found methyl jasmonate and tyrosine can increased the production of active fraction to 5134.73 ± 1166.82 μg / L in the third day. Our results highlight that chemical synthesis or plant tissue culture both can be the platform for producing active ingredients originated from plant. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|